1. Technical Field
The present invention relates to a process of preparation of a chemical compound; and more particularly, to a process of preparation and purification of a proton pump inhibitor.
2. Description of Related Art
Rabeprazole, as represent by Formula I, is one of the proton pump inhibitors of the benzimidazole-type, and is also the common name for 2({[4-(3-Methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)-1H-benzimidazole. The sodium salt of rabeprazole (i.e., rabeprazole sodium) is an inhibitor for the gastric proton pump, which can suppress the secretion of gastric acid via inhibiting the H+, K+ ATPase at the gastric secretory surface of partial cells without effect on cholinergic or histamine H2-receptors. Rabeprazole sodium is usually used in the prescription of the combinatory therapies for the eradication of Helicobacter pylori.

The conventional method for producing rabeprazole is as illustrated in the U.S. Pat. No. 5,045,552. After oxidation with m-chloroperbenzoic acid in dichloromethane at −45° C., quenched with triethylamine, followed by drying over magnesium sulfate, then 2-({[4-(3-Methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)-1H-benzimidazole, namely the rabeprazole acid, is obtained. This crude product is processed by adding to an aqueous sodium hydroxide solution and then distilling twice together with ethanol for the removal of H2O, and finally drying in vacuum. To this end, the final product of rabeprazole sodium is amorphous. Another conventional method disclosed in US2004/0180935A1 to obtain amorphous rabeprazole sodium is to dissolve rabeprazole acid in a mixture of sodium hydroxide in methanol at 25° C.-35° C. and the product is precipitated by adding petroleum ether. The precipitated solid is then filtered, washed and then dried at 50° C.-60° C. for 12 hours.
In order to purify the rabeprazole sodium from the impurities produced in the synthetic process, several methods are used, such as that U.S. Pat. No. 6,180,652 discloses a process for forming the acetone complex of the rabeprazole sodium. This acetone complex, however, is not suitable for the manufacture of medicinal compounds.
There is a need to provide an alternative process for purifying the amorphous rabeprazole sodium, especially in a more convenient and more efficient way than the conventional methods.